Comparison Studies

Four of 11 randomized controlled clinical studies demonstrated that an SSRI reduced suicidal ideation compared to another antidepressant (usually a tricyclic antidepressant) and to placebo (Eberhard et al., 1988; Gonella et al., 1990; Kasper et al., 1995; Montgomery et al., 1978). Venlafaxine, given in a dose that predominantly inhibits the serotonin transporter, showed greater efficacy compared with a tricyclic after up to six weeks of treatment (Mahapatra and Hackett, 1997). Four of the remaining studies found comparable improvement in suicidal ideation with SSRIs and the reference compound (Judd et al., 1993; Lapierre, 1991; Möller and Steinmeyer, 1994; Tollefson et al., 1993). In a comparison of moclobemide, a reversible monoamine oxidase inhibitor, with the SSRI clomipramine, increased suicidality was seen among the moclobemide group but not among the clomipramine group (Danish University Antidepressant Group, 1993).

Possible Adverse Effects of Antidepressants

Mental illness can be incapacitating, and the possibility exists that as the symptoms lift (because of treatment) individuals become more capable of carrying out plans of violence toward self or others. This has been of great concern in the use of antidepressants. Müller-Oerlinghausen and Berghofer (1999) have described situations where antidepressants increase the risk of suicide in some patients by “energizing patients with preexisting suicidal thoughts or inducing akathisa (increased movement with associated anxiety/agitation).” It has long been known that affective disorders can carry a significant risk of suicide, and that some small number of patients will deteriorate rather than improve after being treated with any antidepressant or will become at an increased risk for suicide associated with abrupt improvement.

Case reports have led some investigators to suggest that there may be a risk of emergent suicidality on SSRIs, in particular, fluoxetine. For example, Teicher and colleagues (1990) observed eight patients with major depression and personality disorders who developed suicidal thoughts and in some cases made attempts as their clinical condition deteriorated and fluoxetine was being increased to the 80 mg dosing range. There were several criticisms of these conclusions, including atypical EEG findings in these patients and the persistent increase in dosage as the patients deteriorated.

Healy and colleagues (1999) have outlined several possible mechanisms by which antidepressant medication may lead to suicide in some depressed patients. These proposed mechanisms include antidepressants



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